Role of microRNA dysregulation in Alzheimers Disease

Final Report Summary - MIRNA_AD (Role of microRNA dysregulation in Alzheimers Disease)

Alzheimer's disease is the most common form of dementia. While most of ongoing research is focused on the contribution of Tau and the Amyloid-beta protein, it remains to be investigated to what extent other molecular pathways are involved in the neurodegenerative process underlying the disorder. Recently, microRNAs have been recognized as important regulators of gene expression and their aberrant expresson could lead to perturbation of cellular homeostasis and ultimately to neurodegeneration. However, little is known about the global expression pattern of microRNAs in the brain of patients and the molecular networks potentially regulated by such microRNAs. Moreover, reproducibility of recorded alterations is a major issue. In our study, we found deregulation of a small subset of microRNAs in the hippocampus and prefrontal cortex of Alzheimer's disease patients. We established miR-132-3p as being the most altered microRNA during disease. Down-regulation of miR-132-3p in neuronal cells was inversely correlated with the appearance of the hyper-phosphorylated form of Tau. Additional analysis of miR-132-3p targets points to the FOX transcription factors as regulated by and sharing a common subset of targets with this miRNA. Our results provide the first large scale analysis of microRNAs altered in Alzheimer's disease. When the disease worsens, neuronal cells show lower amount of miR-132-3p and hyper-phosphorylated Tau accumulates in these cells, therefore establishing the down-regulation of miR-132-3p as a new marker of Alzheimer's disease and potentially other neurodegenerative disorders.

Final Report Summary - MIRNA_AD (Role of microRNA dysregulation in Alzheimers Disease)

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